“Wait a minute. You want me to do what?”
That was the first response from Kai Lin, an employee at Mythical Medical, after being asked by senior management to set up a system to proactively oversee “significant change” processes affected by MDR Article 120, Transitional Provision. She was convinced this would be a dead-end, career-limiting, tedious project, and wanted nothing to do with it. Little did she know it would not only be a project that would have enormous, positive implications to millions of patients, but it would become very personal.
In this fictional story, I’ll guide Kai Lin through an active process that provides a framework to address significant change issues that notified bodies and regulators expect.
I will be discussing relevant topics and providing simple, practical clarifications and solutions that can be implemented globally.
Medical Device Coordinating Group and Significant Change
The European Union (EU), Medical Device Regulation (MDR) Article 120(3) Transitional Provision states:
…a device with a certificate that was issued in accordance with Directive 90/385/EEC or Directive 93/42/EEC and which is valid by virtue of paragraph 2 of this Article may only be placed on the market or put into service provided that from the date of application of this Regulation it continues to comply with either of those Directives, and provided there are no significant changes in the design and intended purpose.
In March 2020, the Medical Device Coordination Group (MDCG) published useful guidance to help manufacturers, notified bodies, and competent authorities. It is known as MDRG 2020-3 Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD. See the link below.
https://ec.europa.eu/docsroom/documents/40301
I found the document useful as a framework to have these types of discussions. It outlines situations that would be considered significant changes that would cause medical device certificates to expire with immediate consequences of shifting to MDR re-licensure.
Could This Be A New Opportunity?
After Kai Lin contacted me, I was curious to learn what had caused this fascinating initial response from a credible, known leader with so many previous successes. Unveiling that could begin a journey that could influence hundreds of staff along millions of patients and healthcare professionals for years.
From one perspective, the MDR Article 120 guidance document is a simple, dull, straightforward flowchart outlining what could be a significant change. From another perspective, it opens a fascinating, extensive journey that could launch opportunities for career development, public health protection, improvements in quality of life, and personal growth.
A Brief Discussion During An International Conference
Kai Lin had just come back from eating a large meal with her team earlier this evening. During our first discussion after a long day at this international medical device conference, I discovered that Kai Lin was still bothered by her most recent assignment. “This is a waste of my time. It’s not helping me. It’s not going to be part of my destiny. I don’t care about what I’m doing now. It just doesn’t matter.”
I learned she had not considered the fundamental opportunity within EU MDR Article 120. “Significant change” implies substantial, major, considerable, and sizeable change, both in terms of medical devices generally and behaviors within organizations specifically, e.g., regulatory bodies, notified bodies, manufacturers, patient advocacy groups, and consultants. It was time to dive a little deeper, highlighting opportunities for leadership. Although a calmness settled on her spirit, a carefully appraising eye was evident.
As I went through each section of the guidance document pointing out the human, social cost, or burden if it was not implemented, it gradually but reluctantly became apparent to her. There would be life versus death implications and, in some cases, improvements in quality of life.
Suddenly, Kai Lin started complaining of stomach pains in her upper right part of her abdomen.
She had trouble just sitting, and it did not seem to worsen or change when she moved in her chair.
She started feeling nauseous. Eventually, she was taken to a local emergency or urgent care clinic.
Her destiny tonight would be within a surgical suite.
Significant Change: Related to Intended Purpose
During the transitional period, there are triggers that will directly influence medical device certificates under the current directives. The most obvious one is extending the device’s intended purpose, involving new users or patient populations. This includes changes in clinical use, such as anatomical sites, changes in access sites or deployment methods. It also includes opportunities to generate additional claims linked to broader intended use or medical indications. If significant clinical evidence supports expanding intended purpose, there are patients and healthcare professionals out there today that are waiting for other diagnostic, therapeutic, or monitoring options.
It is important to note that limitations or reductions in intended purpose or intended use due to Post-Market Surveillance (PMS) signals or changes in state-of-the-art is not considered a significant change. Regulators and notified bodies expect manufacturers to monitor PMS data, both passive and active, and make changes to ensure continued safety and performance of devices when used as intended.
Significant Change: Related to Design or Performance Specification
There is renewed focus to make decisions based on evidence and not just the “hope or promise” that medical devices are performing as intended. This means that design changes will require further clinical or usability data to support safety and performance.
For now, see MEDDEV 2.7/1 Rev 4 and MDCG 2020-6 for further guidance on clinical evidence. Ensure senior management knows that new risks will require control measures, including those existing risks being negatively affected by the change. This guidance also highlights the following: change of built-in control mechanism(s), operating principles, source of energy, or alarms.
Significant Change: Related to Software Changes
This is an exciting area for future professional growth. The following are highlighted: new or major changes of software operating systems or any component; new or modified software architecture or database structure, change of an algorithm; a required user input replaced by a software closed-loop algorithm; and new software diagnostic or therapeutic features.
Another feature that is discussed is a new channel of interoperability. Examples are the ability to safely, securely, and effectively exchange and use information among one or more devices, products, technologies, or systems. This includes displaying, storing, interpreting, analyzing, and automatically acting on or controlling another product. It also addresses a new user interface or presentation of data, such as a new format or new dimension or measuring units. There may also be other software changes that impact diagnosis or treatment delivered and that are NOT considered minor by the manufacturer, notified body, or regulatory agency.
This section of the guidance document again gets personal. If there are opportunities for using newer technologies, imaging displays, or decreasing user input to improve safety, then millions of people’s lives could be saved or certainly have their quality of life improved.
Significant Change: Related to Change of a Material
Many manufacturing staff are out of the spotlight yet are performing tasks that potentially have a ripple effect on the safety and performance of products. It is important to note that when decisions are made to change a material of human/animal origin, including the addition of new materials, this now is a significant change.
Furthermore, changes to a material containing a medicinal substance, changes to the medicinal substance itself, changes that may impact the quality, safety, or efficacy of the medicinal substance are also considered significant changes. Moreover, changes in ingredient(s) or material(s) from either existing or new suppliers that do not meet existing specifications are now significant changes.
If your organization is focusing on developing and overseeing quality management systems affecting these processes, you need to be reminded that your job matters. It’s important and has the potential to affect patients and healthcare practitioners worldwide.
Significant Change: Related to Change of Terminal Sterilization Method of Device or Packaging Design with Impact on the Sterilization
Although one of the last steps in a process, choosing a sterilization method is one of the essential steps in developing and putting into service a medical device. At best, using an insufficient or inappropriate sterilization method can prevent your medical device from being approved. At worst, inadequate sterilization can lead to the transmission of infectious diseases causing patient illness and even death. If you think your sterilization work is unimportant, it is certainly not. Your career could mean a magnificent, brilliant medical device may never get the chance to make a difference in the lives of millions.
These are costly processes, and technology is moving faster than expected. The guidance highlights that changes in terminal sterilization methods or design changes that affect or modify the sterility assurance are now considered significant changes.
Processes need to be developed and monitored to assess change in (i) packaging design, which affects functionality, safety, the stability of seal integrity, or (ii) shelf-life change validated by protocols NOT approved by a notified body.
Being involved in sterilization activities positions your staff to be responsible for producing compliant devices that will never face the consequences of an unsterilized product causing preventable injury or death. There may also be substantial financial penalties, lost reputations, and even the ruin of a business. At a minimum, there could be product brand-damaging effects due to recalls from contamination. Yes, your job is significant and critical.
Changes that are Potentially NOT Significant
Many changes can be made that are not considered “significant changes.” Modifications and their implementation will be verified by a notified body either as part of its surveillance activities or following a manufacturer’s submission for prior approval. Some that may not be considered significant changes are shown here. Please note that manufacturers should always remain responsible for providing evidence that all changes do indeed neither affect the design nor the intended purpose. Also, know that guidance is not law. You can deviate, just explain.
Significant Behavior Change
Months later, Kai Lin was well into transforming Mythical Medical processes to set up systems to proactively oversee “significant change” processes identified by EU MDR Article 120. In a follow-up meeting, being curious, I asked her what brought about her significant change in behavior.
Kai Lin said while in the hospital, dawn had broken in a mesmerizing, hypnotic way. She noticed all the devices that were either being considered for her or used on her during her hospital stay. Many of them were made by Mythical Medical.
There were all sorts of imaging devices such as ultrasounds, CT scans, X-rays, and MRIs. There were those devices used for laparoscopy, along with a variety of monitors. That was when it happened. It was suddenly right in front of her. Instantly, she no longer saw only the device names, catalog numbers, SKUs, or part numbers. She saw something more significant.
She continued “I started imagining seeing patient names etched on them too. Actual names of patients that would eventually be benefiting from these and other devices worldwide. Over there I saw Kunal, John, Jim, Tina, Elena, Stella, Robert, Ye, Olive, Haisley, Dewei, Keanu, Weiying, Santiago, Yuan, Jasmine, Violet, Sarah, Astrid, Charli, Henry, Jackson, Sebastian, Laura, Summer, Matthew, Vivian, Sky, Ezra, Azalea, Selena, Julian, Mateo, Anthony, Jaxon Marilyn, Amy, Ingrid, Aaliyah, Gwyneth, Chung, Avanti, Luna, Evelyn, Karen, Adele, Eliza, Kylie, Jake, Wyatt, John, Jack, Luke, Lynn, Calais, and Jae. There were so many, many more names. They slowly became familiar and endearing.
“Each device was no longer a cold, inanimate manufactured object, but a living system designed to either save lives or improve the quality of lives. The devices needed to be nurtured, developed, fashioned, maintained, repaired, and eventually put to sleep when their lifetime had passed. I felt ashamed that I had been so petty and shortsighted.
“Then, at my bedside, there was a very silent, unassuming, ordinary device doing extraordinary work. Its imaginary name, Kai Lin, was attached to my bed rail steadily, reliably monitoring my vital signs. Suddenly, I had imagined in its own quiet, unpretentious way, it began gently whispering, ‘You are alive.’ I think my medication had something to do with this, but I am not sure.
“When I got back to the office, the first group of devices I chose to begin to work with were those within the gastrointestinal group. It became personal. I realized right then that I am not wasting my time. This project was helping me to become a better person and leader. I was thrilled now that monitoring significant changes had become part of my destiny too. I care about what I am doing again. It matters, really it does. The team feels it also.”
Closing Thoughts
Now, more than ever, leaders need to be continuously monitoring not only how devices are performing in the marketplace, but the changes that should occur in the natural course of a device’s lifetime (or life cycle). It directly affects product development decisions, approvals, and future budget investments.
There also exists a need to lead efforts to re-train personnel to pay closer attention to product performance during all phases of product development. Tightening up systems around these activities could become a new opportunity for many.
The significant change law and guidance can be dull and straightforward. Still, it could become a fascinating journey that could launch further career development, public health protection, improvement in the quality of life, and personal growth. Kai Lin knew now that the project would have enormous, positive implications to millions of patients and health care personnel around the world. It would become more than just personal as extraordinary, exceptional times were ahead when her leadership would be questioned.
David R Rutledge, Pharm.D., FCCP, FAHA, President & CEO, Global Strategic Solutions, LLC, Silicon Valley in California. david.rutledge@globalstrategicsolutions.com.
+1 (630) 846-0350 cell. The homepage is www.globalstrategicsolutions.com.